The ferrireductase paraferritin contains divalent metal transporter as well as mobilferrin

Umbreit, Jay N.; Conrad, Marcel E.; Hainsworth, Lucille N.; Simovich, Marcia J.

doi:10.1152/ajpgi.00199.2001

Cited by 19 publications

(12 citation statements)

References 25 publications

(28 reference statements)

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“…This would imply that the role of DMT-1 in the uptake of ferrous iron was not solely due to its pump function. DMT-1 is also found in the protein complex paraferritin inside the cell [38]. In association with paraferritin it was found almost exclusively in the hypoglycosylated 60 kD form.…”

Section: Discussionmentioning

confidence: 92%

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

et al. 2003

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There are two pathways for inorganic iron uptake in the intestine, the ferric pathway, mediated by the key protein mobilferrin, and the ferrous pathway, mediated by DMT-1. Previous studies reported that the amount of DMT-1 increased in the intestinal mucosa in iron deficiency and the increase was seen in the apical portion of the villus of the duodenal mucosa. Mobilferrin did not quantitatively increase but became localized at the cell membrane. However, studies on fresh tissue have not previously been performed and the localization to the microvillae has not been demonstrated. In order to more definitively localize these proteins immunofluorescent and electron microscopic studies were undertaken. Samples were also subjected to biochemical analysis and Western analysis. In iron-deficient animals both DMT-1 and Mobilferrin were concentrated in the apical surface of the villae. Electron microscopy revealed that the majority of this increase in the amount of these proteins near the luminal surface was due to increased binding of the proteins to mucin in vesicles near the surface. A significant portion of the iron transport proteins was localized in the goblet cells and outside the cell in the luminal mucin, as demonstrated by immunofluorescence, electron microscopy, and isolation of the mucin by cesium chloride gradient centrifugation and Western analysis. A new model for the transport of metal ions was suggested. The metal transport proteins travel from vesicles inside the cell out to the lumen mucin. This increases the surface area and allows a greater portion of the lumen contents to be exposed to the binding proteins. Once the metal is bound to the externalized protein it is internalized into the cell. This explains many of the unique properties of the iron-binding proteins and suggests that it may be a more general model for the absorption of other nutrients. Am. J. Hematol. 74:32-45, 2003.

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Section: Discussionmentioning

confidence: 92%

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

et al. 2003

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Section: Iron Dyshomeostasismentioning

confidence: 99%

“…Building on a known FMO-calreticulin complex (65), a ferrireductase role for FMO in an iron import complex termed "paraferritin" was described (66). The complex was further described as including FMO, calreticulin, DMT1, and other proteins (66). Its suggested roles include serving as an alternative, non-transferrin mechanism for cellular iron uptake and as a means to deliver iron to mitochondrial ferrochelatase for incorporation into heme.…”

Section: Iron Dyshomeostasismentioning

confidence: 99%

Flavin-containing monooxygenases in aging and disease: Emerging roles for ancient enzymes

Rossner

Kaeberlein

Leiser

2017

Journal of Biological Chemistry

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Edited by F. Peter GuengerichFlavin-containing monooxygenases (FMOs) are primarily studied as xenobiotic metabolizing enzymes with a prominent role in drug metabolism. In contrast, endogenous functions and substrates of FMOs are less well understood. A growing body of recent evidence, however, implicates FMOs in aging, several diseases, and metabolic pathways. The evidence suggests an important role for these well-conserved proteins in multiple processes and raises questions about the endogenous substrate(s) and regulation of FMOs. Here, we present an overview of evidence for FMOs' involvement in aging and disease, discussing the biological context and arguing for increased investigation into the function of these enzymes.

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“…7) the specific blockade of ferric iron transport by antibodies to ␤ 3 -integrin and the unique specificity for Fe 3ϩ , rather than Fe 2ϩ or other divalent metals that characterize DMT1 (23). However, DMT1 might be part of the integrin-␤ 3 -mobilferrin pathway (118), suggesting that it may modify DMT1 specificity. Whether these components transport iron from the cell surface or from endosomes is presently not clear, because most of these proteins are intracellular (107).…”

Section: Many Solutions To the Problem Of Iron Transportmentioning

confidence: 99%

Iron, lipocalin, and kidney epithelia

Yang

Mori

et al. 2003

American Journal of Physiology-Renal Physiology

125

105

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Brilliant new discoveries in the field of iron metabolism have revealed novel transmembrane iron transporters, novel hormones that regulate iron traffic, and iron's control of gene expression. An important role for iron in the embryonic kidney was first identified by Ekblom, who studied transferrin (Landschulz W and Ekblom P. J Biol Chem 260: 15580-15584, 1985; Landschulz W, Thesleff I, and Ekblom P. J Cell Biol 98: 596-601, 1984; Thesleff I, Partanen AM, Landschulz W, Trowbridge IS, and Ekblom P. Differentiation 30: 152-158, 1985). Nevertheless, how iron traffics to developing organs remains obscure. This review discusses a member of the lipocalin superfamily, 24p3 or neutrophil gelatinase-associated lipocalcin (NGAL), which induces the formation of kidney epithelia. We review the data showing that lipocalins transport low-molecular-weight chemical signals and data indicating that 24p3/NGAL transports iron. We compare 24p3/NGAL to transferrin and a variety of other iron trafficking pathways and suggest specific roles for each in iron transport. metanephric mesenchyme; induction; neutrophil gelatinase-associated lipocalin; NGAL; 24p3; transferrin; embryo THE KIDNEY FORMS FROM THE interaction of an epithelial tubule called the ureteric bud and metanephric mesenchymal cells (103). The ureteric bud produces the collecting ducts, whereas the mesenchymal cells produce the glomeruli and tubules of the nephron. Mesenchymal cells convert into epithelia and form nephrons after receiving signals from the ureteric bud (15,29,42,44,61,71,103,106,115,116,119). The ureteric bud has been shown to control the growth of the mesenchyme (for example, by FGFs) (4, 92), the expression of the essential Wnt-4 gene (for example, by Wnt-6) (60), and the expression of cohorts of epithelial proteins [for example, by leukemia inhibitory factor (LIF)] (6, 95).In this review, we describe a new ureteric bud protein called 24p3 (mouse) or neutrophil gelatinase-associated lipocalcin (NGAL; human) and review its relatives in the lipocalin superfamily. 24p3/NGAL induces epithelial development, but it neither targets the same mesenchymal cells as Wnt-6/Wnt-4 or LIF, nor does it activate the same type of signaling mechanism. We hypothesize that 24p3/NGAL is a novel signaling molecule and iron transporter, and we speculate that it is a new member of the non-transferrin-bound iron pool (NTBI). We describe general mechanisms of iron transport and the settings in which 24p3/NGAL and the NTBI pool are active. Last, we compare iron transport in the developing and adult kidney. Iron metabolism in fetal development is topical: 18% of human pregnancies in the industrialized countries are iron deficient, as are 38-55% of pregnancies in Africa and 62-88% in India, and worldwide the total affected births may near one billion (14). However, because little is known about embryonic mechanisms of iron handling, we have included a number of hypotheses and suggested experiments. 24p3/NGAL INDUCES EPITHELIATo identify novel ureteric bud factors that activate the m...

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The ferrireductase paraferritin contains divalent metal transporter as well as mobilferrin

Cited by 19 publications

References 25 publications

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

Localization of the iron transport proteins mobilferrin and DMT‐1 in the duodenum: The surprising role of mucin

Flavin-containing monooxygenases in aging and disease: Emerging roles for ancient enzymes

Iron, lipocalin, and kidney epithelia

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